There have been recent dramatic advances in our understanding of the molecu
lar mechanisms governing the elaboration of mature tissue-specific cellular
subpopulations from embryonic stem (ES) cells, These investigations have g
enerated a range of new biological and potential therapeutic reagents to al
low us to dissect specific stages of mammalian development that were previo
usly experimentally inaccessible, Ultimately, we will be able to reconstitu
te seminal signaling pathways to promote regeneration of the nervous system
, Totipotent ES cells possess an unlimited proliferative capacity that make
them attractive candidates for use in a series of innovative transplantati
on paradigms. Elucidation of the molecular and physiologic properties of ES
cells also has important implications for our understanding of the integra
tive cellular processes underlying neural induction, patterning of the neur
al tube, neural lineage restriction and commitment, neuronal differentiatio
n, regional neuronal subtype specification, and the specific pathological c
onsequences of alterations in discrete components of these fundamental neur
odevelopmental pathways, In addition, recent experimental observations sugg
est that neurodegenerative disease pathology may involve alterations in a r
ange of progressive neural inductive and neurodevelopmental events through
novel biological mechanisms that result in sublethal impairments in cellula
r homeostasis within evolving regional neuronal precursor populations conta
ining the mutant proteins, culminating in increased vulnerability of their
differentiated neuronal progeny to late-onset apoptosis, Future discoveries
in ES cell research will offer unique conceptual and therapeutic perspecti
ves that represent an alternative to neural stem cell therapeutic strategie
s for ameliorating the pathologic consequences of a broad range of genetic
and acquired insults to the developing, adult, and aging brain, Evolving re
generative strategies for both neurodevelopmental and neurodegenerative dis
eases will likely involve the targeting of vulnerable regional neural precu
rsor populations during "presymptomatic" clinicopathological stages prior t
o the occurrence of irrevocable neural cell injury and cell death, Anat Rec
(New Anat) 265:142-156, 2001, (C) 2001 Wiley-Liss, Inc.